A crystal-clear ingredient for allergy?: Charcot-Leyden crystals (CLCs) are formed from the eosinophil granule protein galectin-10 (Gal10) and found in severe eosinophil-associated diseases like asthma and chronic rhinosinusitis. Whether CLCs actively contribute to disease pathogenesis is unknown. Persson et al. found that lab-grown Gal10 crystals are biosimilar to CLCs (see the Perspective by Allen and Sutherland). When given to mice, the crystals acted as a type 2 adjuvant, mimicking many of the features of human asthma. In contrast, a Gal10 mutein unable to crystallize had no effect. Antibodies against epitopes crucial for Gal10 autocrystallization could dissolve both in vitro–generated Gal10 crystals and patient-derived CLCs. Furthermore, these anti-Gal10 antibodies reversed the effects of Gal10 crystals in a humanized mouse model of asthma, suggesting a potential therapeutic approach for crystallopathies more broadly. Science , this issue p. eaaw4295 ; see also p. 738

The innate immune response is impaired in asthma, with increased epithelial release of C-X-C motif chemokine ligand (CXCL)8, interleukin (IL)-33 and thymic stromal lymphopoietin (TSLP). We hypothesised that dendritic cells might modulate the hyperresponsive epithelium in severe asthma.For this purpose, we investigated epithelial–dendritic crosstalk in normal and diseased conditions, and because ultrafine particulate matter may affect asthmatic airways, we investigated its impact on this crosstalk. Air–liquid interface cultures of human bronchial epithelial cells (HBEC) of control subjects (cHBEC) or severe asthma patients (saHBEC) were co-cultured with monocyte-derived dendritic cells (moDC).Increased release of CXCL8, TSLP and IL-33 from saHBEC contrasted with cHBEC producing CXCL10 and CCL2. Regarding moDC activation, saHBEC co-cultures induced only upregulation of CD86 expression, while cHBEC yielded full moDC maturation with HLA-DR, CD80, CD86 and CD40 upregulation. Particulate matter stimulation of HBEC had no effect on cHBEC but stimulated CXCL8 and IL-33 release in saHBEC. Particulate matter impaired epithelium signalling (TSLP, IL-33 and CXCL8) in saHBEC co-cultures despite C-C chemokine ligand 2 induction.Crosstalk between HBEC and moDC can be establishedin vitro, driving a T1-type response with cHBEC and a T2-type response with saHBEC. Normal or asthmatic status of HBEC differentially shapes the epithelial–dendritic responses. We conclude that control moDC cannot rescue the hyperresponsive airway epithelium of severe asthmatics.

Asthma is a chronic inflammatory airway disorder whose pathophysiological and immunological mechanisms are not completely understood. Asthma exacerbations are mostly driven by respiratory viral infections and characterised by worsening of symptoms. Despite current therapies, asthma exacerbations can still be life-threatening. Natural killer (NK) cells are innate lymphoid cells well known for their antiviral activity and are present in the lung as circulating and resident cells. However, their functions in asthma and its exacerbations are still unclear. In this review, we will address NK cell activation and functions, which are particularly relevant for asthma and virus-induced asthma exacerbations. Then, the role of NK cells in the lungs at homeostasis in healthy individuals will be described, as well as their functions during pulmonary viral infections, with an emphasis on those associated with asthma exacerbations. Finally, we will discuss the involvement of NK cells in asthma and virus-induced exacerbations and examine the effect of asthma treatments on NK cells.

Platelets are small anucleate cells known for their role in haemostasis and thrombosis. In recent years, an increasing number of observations have suggested that platelets are also immune cells and key modulators of immunity. They express different receptors and molecules that allow them to respond to pathogens, and to interact with other immune cells. Platelets were linked to the pathogenesis of some inflammatory disorders including respiratory diseases such as asthma and idiopathic pulmonary fibrosis. Here, we discuss the involvement of platelets in different immune responses, and we focus on their potential role in various chronic lung diseases.